液相合成具有较大空间位阻的N_甲基二肽N__省略__N_Me_L_Ile_O_t.pdfVIP

Liquid-Phase Synthesis of Hindered N-Methyldi- peptide N-Ns-N(Me)-L-Ala-N(Me)-L-Ile-OtBu a a b a b WANG Xiao-Ji * ZHENG Peng-Wu LI Yang DUAN Xue-Min CHEN Li-Gong XU Zheng-Shuang c ( a School of Pharmacy, Jiangxi Science and Technology Normal University, Jiangxi 330013, b c China; School of Chemical Engineering, Tianjin University, Tianjin 300072, China; Laboratory of Chemical Genomics, The Shenzhen Graduate School of Peking University, Shenzhen, 518055, China ) Abstract: The hindered N-methyldipeptide (N-Ns-N(Me)-L-Ala-N(Me)- L-Ile-OtBu), a segment of the new cyclodepsipeptide Apratoxin A[1] , which exhibit cytotoxycity against human tumor cell lines, was synthesized from L-Alanine and L-iso-Leucine through ten steps in overall yield of 49.4%. Keywords: L-Alanine, L-iso-leucine, N-methyldipeptide.1 A N-methylated peptide amide bond often exhibits higher resistance to proteolysis and thus result in improved oral activity and enhanced duration of action[2] . However, few N-Methyl amino acids are commercially available and their synthesis is tedious[3]; the formation of hindered amide bond with high yield and minimal racemization is often troublesome. Inspired by the results of the synthesis of hindered peptides *联系人简介: 王晓季 (1974 年出生), 男, 博士, 教授, 从事药物及天然化合物的合成研究. 电话: 0791-3802393. e-mail: wangxiaoji2000@ 5286 from highly reactive amino acyl chlorides[4] , which was protected